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FDA gives ricin vaccine a shot in the arm

An experimental vaccine developed at UT Southwestern for the prevention of ricin intoxication recently received an orphan drug designation from the Food and Drug Administration (FDA).

RiVax was created by Drs. Ellen Vitetta and Joan Smallshaw, director and assistant professor, respectively, of the Cancer Immunobiology Center. The vaccine has been shown to induce a protective immune response against ricin exposure.

Dr. Vitetta and her colleagues developed the vaccine for the deadly toxin as an outgrowth of their cancer-therapy work.

Dr. Ellen Vitetta

“Orphan drug” status means that a drug will be available on the open market more rapidly than most in development. The FDA grants the designation when a drug is targeted at a small market, vastly exceeds expectations during the experimental trial phase and/or works much better than the placebo given during clinical trials.

Dr. Vitetta called the designation an important milestone for UT Southwestern, which holds the patent on the vaccine.

“This vaccine was developed here and manufactured in the Cancer Immunobiology Center’s Good Manufacturing Process laboratory. The first clinical trial was carried out in volunteers at UT Southwestern,” she said, adding that the National Institutes of Health has funded all the research. “It was an interesting experience that taught us a great deal about many aspects of vaccine development, now a major focus of our center.”

As a recombinant vaccine, RiVax is a form of ricin that consists of a genetically modified subunit of the toxin rather than an inactivated whole toxin. Dr. Vitetta’s team showed in pre-clinical studies that the subunit of the ricin toxin used to make RiVax was entirely nontoxic but retained the capacity to elicit immunity in mice, rabbits and humans. An intramuscular, or intradermal, injection protected mice against aerolized ricin, the most likely route of delivery in a terrorist attack, Dr. Vitetta said.

In addition, in one completed clinical trial, UT Southwestern researchers demonstrated that the vaccine induced neutralizing antibodies in humans. When the human serum was administered to mice, they were protected against ricin exposure.

Dr. Vitetta and her colleagues are now conducting a second trial in which RiVax has been combined with an adjuvant, a formulation that may lengthen the time the vaccine is effective. An adjuvant, such as alum, is an ingredient that enhances the immune response of a stand-alone vaccine. Other common vaccines, such as tetanus, are typically administered with an adjuvant and can confer immunity for years. The trial should be completed in a year.

Ricin, which can be administered in food and water or sprayed as an aerosol, is extracted from castor beans. No approved vaccine exists to prevent ricin poisoning in humans, and the biological agent has a long history of use in espionage. The Centers for Disease Control and Prevention classifies ricin as a “Category B” biological agent, which means it is “relatively easy to disseminate.”

Depending on how the ricin is administered as a poison, victims develop fever, nausea and abdominal pain or lung damage before dying within a few days of exposure. There is no antidote after the first few hours of exposure and, because symptoms do not appear until later and often mimic other illnesses, individuals often do not know they have been exposed until it is too late for treatment, Dr. Vitetta said.

Soligenix, a late-stage pharmaceutical company, has received an exclusive license for RiVax and is developing large-scale manufacturing processes. Company leaders hope to produce a large stockpile for more advanced human clinical testing, product licensing and potential purchases from the U.S. government, primarily military personnel.